Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

PTEN status assessment in the Johns Hopkins active surveillance cohort



Up to half of men with Gleason score 6 (GS6) prostate cancers initially managed with active surveillance (AS) will eventually require definitive therapy, usually due to tumor grade reclassification during follow-up. We examined the association between PTEN status on biopsy and subsequent clinicopathologic outcomes in men with GS6 cancers who enrolled in AS.


We performed a case–control study of men enrolled in the Johns Hopkins AS cohort with diagnostic biopsy tissue available for immunohistochemical (IHC) staining. IHC was performed for PTEN using genetically validated protocols for all patients. Cases included men who underwent grade reclassification to GS ≥ 3 + 4 = 7 on biopsy within 2 years of follow-up (i.e., early reclassification) or reclassification to GS ≥ 4 + 3 = 7 on biopsy or radical prostatectomy during follow-up (i.e., extreme reclassification). Control patients were diagnosed with GS6 cancer and monitored on AS for at least 8 years without undergoing biopsy reclassification.


Among 67 cases with adequate tissue, 31 men underwent early reclassification and 36 men underwent extreme reclassification. Cases were compared to 65 control patients with adequate tissue for assessment. On initial prostate biopsy, cases were older (median age 67 vs. 65, p = 0.024) and were less likely to meet very-low-risk criteria (64 vs 79%, p = 0.042) as compared to controls. Although not statistically significant, PTEN loss was observed in only 1 (1.5%) of 65 controls as compared to 6 (9%) of 67 cases (p = 0.062).


PTEN loss was rare among men with GS6 prostate cancer enrolled in AS at Johns Hopkins. Despite this, PTEN loss was more frequent among men who underwent early or extreme reclassification to higher-grade cancer as compared to controls. Additional studies in larger low-risk cohorts may better elucidate a potential role for PTEN in selecting patients for AS.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1


  1. 1.

    Tosoian JJ, Loeb S, Epstein JI, Turkbey B, Choyke PL, Schaeffer EM. Active surveillance of prostate cancer: use, outcomes, imaging, and diagnostic tools. Am Soc Clin Oncol Educ Book. 2016;35:e235–5.

    Article  Google Scholar 

  2. 2.

    Nassiri N, Margolis DJ, Natarajan S, Sharma DS, Huang J, Dorey FJ, et al. Targeted biopsy to detect Gleason score upgrading during active surveillance for men with low versus intermediate risk prostate cancer. J Urol. 2017;197(3 Pt 1):632–9.

    Article  Google Scholar 

  3. 3.

    Ma TM, Tosoian JJ, Schaeffer EM, Landis P, Wolf S, Macura KJ, et al. The role of multiparametric magnetic resonance imaging/ultrasound fusion biopsy in active surveillance. Eur Urol. 2017;71:174–80.

    Article  Google Scholar 

  4. 4.

    Jamaspishvili T, Berman DM, Ross AE, Scher HI, De Marzo AM, Squire JA, et al. Clinical implications of PTEN loss in prostate cancer. Nat Rev Urol. 2018;15:222–34.

    CAS  Article  Google Scholar 

  5. 5.

    Lotan TL, Gurel B, Sutcliffe S, Esopi D, Liu W, Xu J, et al. PTEN protein loss by immunostaining: analytic validation and prognostic indicator for a high risk surgical cohort of prostate cancer patients. Clin Cancer Res. 2011;17:6563–73.

    CAS  Article  Google Scholar 

  6. 6.

    Lotan TL, Carvalho FL, Peskoe SB, Hicks JL, Good J, Fedor HL, et al. PTEN loss is associated with upgrading of prostate cancer from biopsy to radical prostatectomy. Mod Pathol. 2015;28:128–37.

    CAS  Article  Google Scholar 

  7. 7.

    Lotan TL, Wei W, Morais CL, Hawley ST, Fazli L, Hurtado-Coll A, et al. PTEN loss as determined by clinical-grade immunohistochemistry assay is associated with worse recurrence-free survival in prostate cancer. Eur Urol Focus. 2016;2:180–8.

    Article  Google Scholar 

  8. 8.

    Lotan TL, Heumann A, Rico SD, Hicks J, Lecksell K, Koop C, et al. PTEN loss detection in prostate cancer: comparison of PTEN immunohistochemistry and PTEN FISH in a large retrospective prostatectomy cohort. Oncotarget. 2017;8:65566–76.

    PubMed  PubMed Central  Google Scholar 

  9. 9.

    Ahearn TU, Pettersson A, Ebot EM, Gerke T, Graff RE, Morais CL. et al. A prospective investigation of PTEN loss and ERG expression in lethal prostate cancer. J Natl Cancer Inst. 2015;108:pii: djv346

    Article  Google Scholar 

  10. 10.

    Ferraldeschi R, Nava Rodrigues D, Riisnaes R, Miranda S, Figueiredo I, Rescigno P, et al. PTEN protein loss and clinical outcome from castration-resistant prostate cancer treated with abiraterone acetate. Eur Urol. 2015;67:795–802.

    CAS  Article  Google Scholar 

  11. 11.

    Reid AH, Attard G, Ambroisine L, Fisher G, Kovacs G, Brewer D, et al. Molecular characterisation of ERG, ETV1 and PTEN gene loci identifies patients at low and high risk of death from prostate cancer. Br J Cancer. 2010;102:678–84.

    CAS  Article  Google Scholar 

  12. 12.

    Mithal P, Allott E, Gerber L, Reid J, Welbourn W, Tikishvili E, et al. PTEN loss in biopsy tissue predicts poor clinical outcomes in prostate cancer. Int J Urol. 2014;21:1209–14.

    CAS  Article  Google Scholar 

  13. 13.

    Lotan TL, Wei W, Ludkovski O, Morais CL, Guedes LB, Jamaspishvili T, et al. Analytic validation of a clinical-grade PTEN immunohistochemistry assay in prostate cancer by comparison with PTEN FISH. Mod Pathol. 2016;29:904–14.

    CAS  Article  Google Scholar 

  14. 14.

    Lokman U, Erickson AM, Vasarainen H, Rannikko AS, Mirtti T. PTEN loss but not ERG expression in diagnostic biopsies is associated with increased risk of progression and adverse surgical findings in men with prostate cancer on active surveillance. Eur Urol Focus 2017.

  15. 15.

    Tosoian JJ, Mamawala M, Patel HD, Alam R, Epstein JI, Ross AE, et al. Tumor volume on biopsy of low risk prostate cancer managed with active surveillance. J Urol. 2018;199:954–60.

    Article  Google Scholar 

  16. 16.

    Epstein JI, Allsbrook WC Jr, Amin MB, Egevad LL, Committee IG. The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. Am J Surg Pathol. 2005;2:1228–42.

    Article  Google Scholar 

  17. 17.

    Klotz L, Vesprini D, Sethukavalan P, Jethava V, Zhang L, Jain S, et al. Long-term follow-up of a large active surveillance cohort of patients with prostate cancer. J Clin Oncol. 2015;33:272–7.

    Article  Google Scholar 

  18. 18.

    Welty CJ, Cowan JE, Nguyen H, Shinohara K, Perez N, Greene KL, et al. Extended followup and risk factors for disease reclassification in a large active surveillance cohort for localized prostate cancer. J Urol. 2015;193:807–11.

    Article  Google Scholar 

  19. 19.

    Godtman RA, Holmberg E, Khatami A, Pihl CG, Stranne J, Hugosson J. Long-term results of active surveillance in the Göteborg Randomized, Population-based Prostate Cancer Screening Trial. Eur Urol. 2016;70:760–6.

    Article  Google Scholar 

  20. 20.

    Tosoian JJ, Mamawala M, Epstein JI, Landis P, Wolf S, Trock BJ, et al. Intermediate and longer-term outcomes from a prospective active-surveillance program for favorable-risk prostate cancer. J Clin Oncol. 2015;33:3379–85.

    Article  Google Scholar 

  21. 21.

    Cooperberg MR, Carroll PR. Trends in management for patients with localized prostate cancer, 1990-2013. JAMA. 2015;314:80–82.

    CAS  Article  Google Scholar 

  22. 22.

    National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Prostate Cancer (Version 4.2018). Accessed September 19, 2018.

  23. 23.

    Nguyen PL, Haddad Z, Ross AE, Martin NE, Deheshi S, Lam LLC, et al. Ability of a genomic classifier to predict metastasis and prostate cancer-specific mortality after radiation or surgery based on needle biopsy specimens. Eur Urol. 2017;72:845–52.

    Article  Google Scholar 

  24. 24.

    Nguyen PL, Shin H, Yousefi K, Thompson DJ, Hornberger J, Hyatt AS, et al. Impact of a genomic classifier of metastatic risk on postprostatectomy treatment recommendations by radiation oncologists and urologists. Urology. 2015;86:35–40.

    Article  Google Scholar 

  25. 25.

    Klein EA, Santiago-Jimenez M, Yousefi K, Robbins BA, Schaeffer EM, Trock BJ, et al. Molecular analysis of low grade prostate cancer using a genomic classifier of metastatic potential. J Urol. 2017;197:122–8.

    CAS  Article  Google Scholar 

  26. 26.

    Tosoian JJ, Chappidi MR, Bishoff JT, Freedland SJ, Reid J, Brawer M, et al. Prognostic utility of biopsy-derived cell cycle progression score in patients with National Comprehensive Cancer Network low-risk prostate cancer undergoing radical prostatectomy: implications for treatment guidance. BJU Int. 2017;120:808–14.

    CAS  Article  Google Scholar 

  27. 27.

    Leapman MS, Cowan JE, Nguyen HG, Shinohara KK, Perez N, Cooperberg MR, et al. Active surveillance in younger men with prostate cancer. J Clin Oncol. 2017;35:1898–904.

    Article  Google Scholar 

  28. 28.

    Bokhorst LP, Valdagni R, Rannikko A, Kakehi Y, Pickles T, Bangma CH, et al. A decade of active surveillance in the PRIAS Study: an update and evaluation of the criteria used to recommend a switch to active treatment. Eur Urol. 2016;70:954–60.

    Article  Google Scholar 

  29. 29.

    Tretiakova MS, Wei W, Morais CL, Feng Z, McKenney JK, Simko J, et al. Increased proliferative rate and PTEN loss in prostate cancer are correlated and both associated with risk of recurrence in multivariate models. Mod Pathol. 2016;29:267A.

    Google Scholar 

  30. 30.

    Guedes LB, Tosoian JJ, Hicks J, Ross AE, Lotan TL. PTEN loss in Gleason Score 3+4=7 prostate biopsies is associated with nonorgan confined disease at radical prostatectomy. J Urol. 2017;197:1054–9.

    Article  Google Scholar 

  31. 31.

    Baena-Del Valle JA, Zheng Q, Hicks JL, Fedor H, Trock BJ, Morrissey C, et al. Rapid loss of RNA detection by in situ hybridization in stored tissue blocks and preservation by cold storage of unstained slides. Am J Clin Pathol. 2017;148:398–415.

    Article  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Tamara L. Lotan.

Ethics declarations


Funding for this research was provided in part by a Transformative Impact Award from the CDMRP (W81XWH-13-2-0070, to TLL), the Patrick Walsh Prostate Cancer Research Fund, and NCI Cancer Center Support Grant 5P30CA006973.

Conflict of interest

TLL has received research support from Ventana Medical Systems.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Tosoian, J.J., Guedes, L.B., Morais, C.L. et al. PTEN status assessment in the Johns Hopkins active surveillance cohort. Prostate Cancer Prostatic Dis 22, 176–181 (2019).

Download citation

Further reading


Quick links